1. Field of the Invention
This invention relates to a method and apparatus for reducing diffusion/scattering of light through turbid samples.
2. Description of the Related Art
Optical methods for imaging and targeted medical treatment (e.g. photodynamic therapy (PDT)) are attractive because they are versatile, non-ionizing and relatively cheap (compared to MRI, SPECT, x-ray etc). However, despite the impressive progress in the field of optics, tissue scattering of light presents a major road block in applying these optical methods in deep tissues. Generally, light spreads in tissue, due to diffusion, to an extent that is about several times the thickness of the tissue. As a result, resolution of optical methods rapidly decreases as the thickness of the tissue increases. Also, as light diffuses, the amount of energy is also spread over the area of diffusion. Thus, light with increasingly high energy is required at the entrance side for excitation of fluorophores or PDT agents, for example, in deep tissues. This eventually leads to tissue damage and is therefore impractical and unsafe. In other words, if the tissue scattering problem can be overcome, to deliver focused light to deep tissues, one of the most important barriers in the more widespread utilization of light in biomedical imaging will have been torn down.
Although several methods to overcome the problem of tissue scattering have been proposed, these methods are only able to refocus light through a piece of tissue, but not controllably within the tissue. One of the methods, proposed by Allard Mosk et. al. and illustrated in FIG. 1, uses a spatial light modulator (SLM) to iteratively tailor a wavefront 100 to come to a focus 102 [1]. FIG. 1 illustrates how the initial wavefront 100 of the light 102 incident on an opaque, strongly scattering turbid medium 104 (e.g., TiO¬2) pigment) is scattered to form diffuse light 106 and does not penetrate deeply into the sample 104. However, like any iterative method, a feedback is required. Mosk's method depends on tracking the fluorescence emitted by a fluorescence bead 106 for feedback control, and using the feedback from the fluorescence bead 108 to tailor the wavefront 100 into a tailored wavefront 110, forming less diffuse light 112, thereby focusing and penetrating the light 112 more deeply into the sample 104. (FIG. 1 is based on the cartoon depiction on page 1107 of the publication entitled “the most transparent research,” Nature medicine, Volume 15, Number 10, October 2008).
It is apparent that this method has yet to address several impediments that prevent its direct application to biomedical applications. Firstly, this method will not work if there is a fairly homogenous distribution of fluorophores 104 throughout the sample, since it is then impossible to select the fluorophore 104 to focus to. Secondly, it is impossible to determine the location of the fluorophore even if focusing is achieved (assuming that it is unlikely that the biological tissue has fluorophores concentrated, rather than diffused, in a small area). In other words, this method will only work on specific samples with a concentrated area of fluorophores and a pre-knowledge of the fluorophore location.
One or more embodiments of the present invention detail an idea that combines acousto-optic interaction with the wavefront optimization described by Mosk's group [1] to achieve light focusing in deep tissues, thus finally overcoming an important problem in biomedical optics.